We have read with great interest the article by Romero R, et al. about a preliminary study of metabolomics in premature labor [Citation1]. The authors state that metabolic profiling of the amniotic fluid can be used to assess the risk of preterm delivery in the presence or absence of infection/inflammation. Indeed, there is a great need for a stereotypic pattern of metabolites that will be identified in clinical groups with different outcomes. The authors have investigated certain parameters of metabolomics of amniotic fluid.
We would like to ask the authors whether the current method of study of the amniotic fluid metabolomics is rapid and safe for not only high-risk groups of pregnant but also full-term pregnant with no other pathologic condition. Another question that rises from this study is about the correlation and accuracy of other biological materials, such as maternal plasma with the current specimen of the study. This method seems to be an important diagnostic and assessment tool for understanding the fetal metabolism. The article of Romero R et al. is an important study that investigates a new area of fetal investigation and a point of further discussion.
References
- Romero R, Mazaki-Tovi S, Vaisbuch E, Kusanovic JP, Chaiworapongsa T, Gomez R, Nien JK, Yoon BH, Mazo M, Luo J, et al. Metabolomics in premature labor: a novel approach to identify patients at risk for preterm delivery. J Matern Fetal Neonatal Med 2010; doi: 10.3109/14767058.2010.482618.
Author's reply
Roberto Romero1
John Ryals2
1Chief, Perinatology Research Branch,Program Director for Perinatal Research and Obstetrics, Intramural Division, NICHD, NIH, DHHS, Professor, Molecular Obstetrics and Genetics, Center for Molecular Medicine and Genetics, Wayne State University, Professor of Epidemiology, Michigan State University
2President and CEOMetabolon, Inc.
We would like to thank Dr. Dokos and Dr. Tsakalidis for their interest in our work and publication describing a study of metabolomics to identify biomarkers in the amniotic fluid of women in preterm labor which predict outcome in the presence or absence of intra-amniotic infection/inflammation [Citation1].
Metabolomics and other high-dimensional biology approaches (genomics, transcriptomics, metabolomics, lipidomics, glycomics, etc.) [Citation2,Citation3] represent discovery platforms to identify differences in the composition of biological samples (e.g. serum or plasma, urine, cerebrospinal fluid, amniotic fluid, tissues, etc.) among patients, typically between healthy individuals and those with disease [Citation4–7]. However, high-dimensional biology techniques could also be used to classify patients with a particular clinical entity into those with good and bad prognosis [Citation8], or even uncover the degree of heterogeneity of a particular entity [Citation9]. In the case of our study, we examined the amniotic fluid metabolome among women with preterm labor who delivered at term and those who delivered preterm with and without intra-amniotic infection/inflammation.
High-dimensional biology techniques are not generally designed to be rapid methods, but rather, to be comprehensive in obtaining the best possible description of the composition of a biological fluid. However, once a biomarker (or a set of biomarkers) is identified using discovery platforms, targeted assays can be developed to detect such specific differences [Citation5,Citation6,Citation10]. The purpose of our study and article was to demonstrate that metabolomics allows the detection of differences in the composition of women in the three different clinical groups. It is noteworthy that we report the results of two different studies - the first was an exploratory study, and the second confirmed that metabolomics could indeed discover changes in the composition in the two groups.
In regards to safety, amniotic fluid analysis is processed in the laboratory, and therefore, there are no risks to patients. Metabolomics can be performed in a range of biological fluids including maternal serum, urine and vaginal fluid; therefore, Drs. Dokos and Tsakalidis raise a very pertinent question because future studies should include these biological samples (which are relatively easy to obtain, compared to amniotic fluid). Studies are in progress in our Branch to evaluate high-dimensional biology techniques in the "great obstetrical syndromes". We believe that these techniques can also be helpful in neonatology.
Reference
- Romero, R, Mazaki-Tovi, S, Vaisbuch, E, Kusanovic, JP, Chaiworapongsa, T, Gomez, R, Nien, JK, Yoon, BH, Mazor, M, Luo, J, Banks, D, Ryals, J, Beecher, C. Metabolomics in premature labor: a novel approach to identify patients at risk for preterm delivery. J Matern.Fetal Neonatal Med 2010;23:1344–1359.
- Romero, R, Espinoza, J, Gotsch, F, Kusanovic, JP, Friel, LA, Erez, O, Mazaki-Tovi, S, Than, NG, Hassan, S, Tromp, G. The use of high-dimensional biology (genomics, transcriptomics, proteomics, and metabolomics) to understand the preterm parturition syndrome. BJOG. 2006;113 Suppl 3:118–135.
- Romero, R and Tromp, G. High-dimensional biology in obstetrics and gynecology: functional genomics in microarray studies. Am J Obstet Gynecol 2006;195:360–363.
- Romero, R, Espinoza, J, Rogers, WT, Moser, A, Nien, JK, Kusanovic, JP, Gotsch, F, Erez, O, Gomez, R, Edwin, S, Hassan, SS. Proteomic analysis of amniotic fluid to identify women with preterm labor and intra-amniotic inflammation/infection: the use of a novel computational method to analyze mass spectrometric profiling. J Matern.Fetal Neonatal Med 2008;21:367–388.
- Bujold, E, Romero, R, Kusanovic, JP, Erez, O, Gotsch, F, Chaiworapongsa, T, Gomez, R, Espinoza, J, Vaisbuch, E, Mee, KY, Edwin, S, Pisano, M, Allen, B, Podust, VN, Dalmasso, EA, Rutherford, J, Rogers, W, Moser, A, Yoon, BH, Barder, T. Proteomic profiling of amniotic fluid in preterm labor using two-dimensional liquid separation and mass spectrometry. J Matern.Fetal Neonatal Med 2008;21:697–713.
- Romero, R, Kusanovic, JP, Gotsch, F, Erez, O, Vaisbuch, E, Mazaki-Tovi, S, Moser, A, Tam, S, Leszyk, J, Master, SR, Juhasz, P, Pacora, P, Ogge, G, Gomez, R, Yoon, BH, Yeo, L, Hassan, SS, Rogers, WT. Isobaric labeling and tandem mass spectrometry: a novel approach for profiling and quantifying proteins differentially expressed in amniotic fluid in preterm labor with and without intra-amniotic infection/inflammation. J Matern.Fetal Neonatal Med 2010;23:261–280.
- Gravett, MG, Novy, MJ, Rosenfeld, RG, Reddy, AP, Jacob, T, Turner, M, McCormack, A, Lapidus, JA, Hitti, J, Eschenbach, DA, Roberts, CT Jr., Nagalla, SR. Diagnosis of intra-amniotic infection by proteomic profiling and identification of novel biomarkers. JAMA 2004;292:462–469.
- Rasanen, J, Girsen, A, Lu, X, Lapidus, JA, Standley, M, Reddy, A, Dasari, S, Thomas, A, Jacob, T, Pouta, A, Surcel, HM, Tolosa, JE, Gravett, MG, Nagalla, SR. Comprehensive maternal serum proteomic profiles of preclinical and clinical preeclampsia. J Proteome.Res. 2010;9:4274–4281.
- Tarca, AL, Draghici, S, Romero, R. Developing classifiers for the detection of cancer using multi-analytes. Methods Mol.Biol. 2009;520:259–272.
- Kusanovic, JP, Romero, R, Mazaki-Tovi, S, Chaiworapongsa, T, Mittal, P, Gotsch, F, Erez, O, Vaisbuch, E, Edwin, SS, Than, NG, Camacho, N, Pacora, P, Rogers, W, Hassan, SS. Resistin in amniotic fluid and its association with intra-amniotic infection and inflammation. J Matern.Fetal Neonatal Med 2008;21:902–916.